Efficient Ni (II) transport through a polymer inclusion membrane (PIM) was achieved. A central composite design (DCC) coupled to a Derringer’s desirability function (DF) was used to optimize membrane composition using Kelex 100 (HQ) as carrier, cellulose triacetate (CTA) as polymer support, and tris(2-ethylhexyl) phosphate (TEHP) as plasticizer. The effect of components’ contents in the membrane and the interactions among them on Ni (II) migration was evaluated using two normalized function as response variables (GFeed, GStrip). Using the optimal membrane composition, (96 ± 1.5) % of Ni (II) was detected in the strip solution after 48 h of pertraction. The efficiency factors of the system were determined, i.e., permeability (optimization pH of the aqueous samples and initial metal concentration), selectivity (among Zn (II), Pb (II), Cu (II), Ca (II) and Mg (II)), and stability (reuse capability). Ni (II) transport mechanism was proposed and analyzed as well.